Hypothesis. The basis for a proportion of mammalian developmental errors is the failure of essential loci to be transcribed into mRNA and translated into protein at some critical moment during embryonic life as result of preemption of the transcriptional and translational machinery of the cell at that time by induction of the so-called heat-shock response (HSR). Experimental. Evidence pertaining to the embryonic stress hypothesis of teratogenesis (just stated) will be sought by studying heat-shock protein (HSP) induction in mouse embryos: (i) The ability of mouse tissues at various stages of development to make the HSR will be determined. (ii) Teratogenic agents, both known and suspected, will be examined for their ability to reach the embryo and induce the HSR during organogenesis (e.g., hyperthermia, ethanol and acetaldehyde, thalidomide, aspirin). (iii) The incidence and types of developmental defects in fetuses in which the HSR had been induced during the embryonic period will be determined. Significance. Induction of the HSR during the critical period of organogenesis could constitute a common pathway by which diverse physical and chemical agents would cause similar malformations, the variety and specificity of the defects depending on the developmental stage that had been reached when the response was induced, and on the duration of the response, rather than on the agent itself.